Phenotype conversion from rheumatoid arthritis to systemic lupus erythematosus by introduction of Yaa mutation into FcγRIIB-deficient C57BL/6 mice

Shinya Kawano, Qingshun Lin, Hirofumi Amano, Toshiyuki Kaneko, Keiko Nishikawa, Hiromichi Tsurui, Norihiro Tada, Hiroyuki Nishimura, Toshiyuki Takai, Toshikazu Shirai, Yoshinari Takasaki, Sachiko Hirose

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

We previously established an IgG Fc receptor IIB (FcγRIIB)-deficient C57BL/6 (B6)-congenic mouse strain (KO1), which spontaneously develops rheumatoid arthritis (RA), but not systemic lupus erythematosus (SLE). Here, we show that when Y chromosome-linked autoimmune acceleration (Yaa) mutation was introduced in KO1 strain (KO1.Yaa), the majority of KO1.Yaa mice did not develop RA, but instead did develop SLE. This phenotype conversion did not depend on autoantibody specificity, since KO1.Yaa mice, compared with KO1, showed a marked increase in serum levels of both lupus-related and RA-related autoantibodies. The increase in frequencies of CD69+ activated B cells and T cells, and the spontaneous splenic GC formation with T follicular helper cell generation were manifest early in life of KO1.Yaa, but not KO1 and B6.Yaa, mice. Activated CD4+ T cells from KO1.Yaa mice showed upregulated production of IL-21 and IL-10, compared with the finding in KO1 mice, indicating the possibility that this aberrant cytokine milieu relates to the disease phenotype conversion. Thus, our model is useful to clarify the shared and the disease-specific mechanisms underlying the clinically distinct systemic autoimmune diseases RA and SLE.

Original languageEnglish
Pages (from-to)770-778
Number of pages9
JournalEuropean Journal of Immunology
Volume43
Issue number3
DOIs
Publication statusPublished - 2013 Mar

Keywords

  • Cytokines
  • FcγRIIB receptor
  • Rheumatoid arthritis
  • Systemic lupus erythematosus
  • Yaa mutation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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